c-di-GMP通过向转录抑制剂NadRR来调节细菌NAD生物合成
Lianying Mao1, Jialin Li1, Xinyi Huo1
1State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
mBio
|August 18, 2025
概括
循环二-GMP (c-di-GMP) 激活NadR,这是一个调节沙门氏菌中NAD合成的蛋白质. 这种相互作用提高了NAD的产生,并增强了细菌DNA的抗损伤能力.
科学领域:
- 细菌生理学 细菌生理学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 循环二-GMP (c-di-GMP) 是一种关键的细菌第二信使,调节各种生理过程.
- 尼古丁胺胺氨基二核酸 (NAD) 对细胞功能至关重要,细菌采用各种机制来控制其代谢.
- 在此之前,c-di-GMP信号传递与细菌NAD代谢之间的联系尚未被探索.
研究的目的:
- 确定新的c-di-GMP效应剂,并探索其生理作用.
- 为了研究c-di-GMP信号传递和细菌中NAD代谢之间的联系.
- 将NadR描述为NAD稳态的c-di-GMP响应调节器.
主要方法:
- 使用c-di-GMP/转录因子结合屏幕来识别潜在的作用因子.
- 生物化学测试用于确认c-di-GMP与Nadr结合及其对DNA结合的影响.
- 进行了酶活性测定,以评估NadR的尼古丁胺胺单核酸腺转移酶和利博尼古丁胺胺激酶活性.
主要成果:
- 纳德R是NAD合成和救援基因的抑制剂,被确定为*Salmonella enterica*血清Typhimurium中的c-di-GMP响应转录因子.
- c-di-GMP以高 afinity 与 NadR 结合,抑制其 DNA 结合,并上调 NAD 合成和救援基因.
- c-di-GMP还刺激了NadR的酶活性,导致NAD合成增加,并增强了*S*中的DNA损伤抵抗力. 这是一个 Typhimurium.
- 其他肠杆菌物种的NadR也感知到c-di-GMP,这表明了一个保存的调节机制.
结论:
- 这项研究揭示了一种新的调节途径,即c-di-GMP通过Nadr调节细菌NAD代谢.
- 这种机制通过增加细胞内NAD水平来增强细菌对DNA损伤的抵抗力.
- 这些发现扩大了对c-di-GMP多样化的生理作用的理解,并突出了Enterobacterales中保存的调节策略.
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